Published on Web 10/07/2010
Allylic C-H Acetoxylation with a 4,5-Diazafluorenone-Ligated Palladium Catalyst: A Ligand-Based Strategy To Achieve Aerobic Catalytic Turnover Alison N. Campbell, Paul B. White, Ilia A. Guzei, and Shannon S. Stahl* Department of Chemistry, UniVersity of Wisconsin-Madison, 1101 UniVersity AVenue, Madison, Wisconsin 53706, United States Received July 1, 2010; E-mail:
[email protected] Abstract: Pd-catalyzed C-H oxidation reactions often require the use of oxidants other than O2. Here we demonstrate a ligandbased strategy to replace benzoquinone with O2 as the stoichiometric oxidant in Pd-catalyzed allylic C-H acetoxylation. Use of 4,5-diazafluorenone (1) as an ancillary ligand for Pd(OAc)2 enables terminal alkenes to be converted to linear allylic acetoxylation products in good yields and selectivity under 1 atm O2. Mechanistic studies have revealed that 1 facilitates C-O reductive elimination from a π-allyl-PdII intermediate, thereby eliminating the requirement for benzoquinone in this key catalytic step.
The selective oxidation of C-H bonds in organic molecules is an important and growing field.1 Many of the emerging methods utilize palladium catalysts in combination with stoichiometric organic or transition-metal oxidants, such as PhI(OAc)2, benzoquinone, CuII, or AgI.2 Mechanistic studies have suggested that these oxidizing agents often react with organopalladium(II) intermediates and promote reductive elimination of carbon-carbon or carbonheteroatom bonds.3 Replacement of these oxidants with molecular oxygen represents a significant fundamental challenge that has important implications for environmentally benign, large-scale applications of these methods.4,5 Here we present a ligand-based strategy to replace benzoquinone (BQ) with O2 as an oxidant in Pd-catalyzed allylic C-H acetoxylation reactions. Preliminary mechanistic studies have revealed that the use of 4,5-diazafluorenone (1) as an ancillary ligand facilitates C-O bond formation from π-allyl-PdII species and thereby permits O2 to be used as the oxidant in a PdII/Pd0 catalytic cycle, eliminating the requirement for BQ.6
Pd-catalyzed allylic acetoxylation reactions represent a prominent class of C-H oxidations that have been the subject of extensive historical7 and contemporary8,9 interest. The vast majority of these reactions utilize BQ as a stoichiometric or cocatalytic oxidant. Fundamental studies have implicated at least three possible roles for BQ in the catalytic mechanism (Scheme 1): (1) promotion of nucleophilic attack by acetate on a π-allyl-PdII species (step II);3a,d (2) displacement of the allylic acetate product from Pd0 following reversible C-O bond formation (step III);8d and (3) oxidation of Pd0 to PdII (step IV).10 Because molecular oxygen is also capable of oxidizing Pd0 to PdII,6 we reasoned that an aerobic allylic C-H oxidation process could be achieved by identifying a ligand for Pd that could eliminate the requirement for BQ in steps II and III. Pyridine, phenanthroline (phen), and related nitrogenous ligands have been widely used in Pd-catalyzed aerobic oxidation reactions.11 15116
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Scheme 1. Proposed Mechanism for Palladium-Catalyzed Allylic Acetoxylation
Table 1. Identification of a Ligand for Palladium-Catalyzed Aerobic
Allylic Acetoxylationa
a Conditions: 5% Pd(OAc)2 (3 mg, 0.0134 mmol), 5% ligand (0.0134 mmol), allylbenzene (35 µL, 0.268 mmol), AcOH (1 mL), 1 atm O2, 80 °C, 18 h. b GC yields (internal standard ) nitrobenzene). c Here 10% ligand was used.
Such ligands were tested recently by Lin, Labinger, and Bercaw in allylic acetoxylation reactions,8d and a bipyrimidine-Pd(OAc)2 catalyst was shown to be effective with 2 equiv of BQ as the 10.1021/ja105829t 2010 American Chemical Society
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oxidant. We reevaluated ligands of this type under 1 atm O2 to test their ability to support aerobic Pd-catalyzed acetoxylation of allylbenzene (Table 1). Pyridine (entry 2), bipyridine (bpy, entry 3), phen (entry 8), bipyrimidine (bpm, entry 11), and a number of bpy and phen derivatives (entries 4-7, 9, and 10) were almost completely ineffective; mostly unreacted allylbenzene was obtained at the end of the reaction. The lack of Pd black in these reactions suggested that the problem is a lack of reactivity rather than catalyst decomposition. A noteworthy exception to these poor results was obtained with 4,5-diazafluorenone (1), which led to an 81% yield of the linear acetoxylation product (entry 12). This ligand was included in the screen on the basis of the hypothesis that the carbonyl group could promote back-bonding from the PdII center. We reasoned that the contribution from the PdIV resonance structure (eq 1) might facilitate C-O reductive elimination from a π-allyl-PdII intermediate and enable BQ-free catalytic turnover (cf. Scheme 1, step II). Subsequent control experiments failed to validate this hypothesis, however. For example, use of di-2-pyridyl ketone (2), another ligand capable of back-bonding, afforded the allylic acetoxylation product in only 5% yield, whereas use of another diazafluorene ligand, 3, in which the carbonyl group in 1 was replaced with two methyl substituents, resulted in a moderate yield of the acetoxylation product (50%). The latter result was not as good as the acetoxylation yield obtained with 1 but was substantially better than the yield with 2 or the other ligands in Table 1. These results suggest that the geometric properties of 1 (e.g., the bite angle) rather than back-bonding underlie the effectiveness of this ligand.
Successful aerobic acetoxylation of allylbenzene provided the basis for further optimization of the reaction conditions and evaluation of the substrate scope. It was possible to decrease the temperature to 60 °C and replace AcOH with dioxane as the reaction solvent; the optimized conditions featured 5 mol % Pd(OAc)2, 16 equiv of AcOH, and a catalytic amount of NaOAc (20 mol %) under 1 atm O2 (see the Supporting Information for additional optimization data). These Pd-catalyzed allylic acetoxylation conditions were then tested with a number of other alkenes (Table 2). Successful reactivity was observed with the naturally occurring allylbenzene derivatives estragole and methyl eugenol (entries 2 and 3) as well as simple hydrocarbon-based R-olefins (entries 4 and 5). Silyl ethers were well-tolerated, as were esters, acetals, amides, and carbamates (entries 6-11). Nearly all of the substrates examined produced the linear acetoxylation product exclusively in good yield and exhibited a strong preference for formation of the E isomer of the alkene. The reactivity appeared to be selective for terminal olefins, as β-methylstyrene, cyclohexene, methyl crotonate, and methylenecyclohexane gave little to no desired product. These allylic oxidation reactions enable anti-Markovnikov hydration of R-olefins to be achieved via tandem O2/H2-coupled redox steps. This net transformation represents a long-standing challenge in the field of catalysis,12 and it can be achieved in a straightforward one-pot process consisting of Pd-catalyzed allylic acetoxylation,
Table 2. Aerobic Allylic Acetoxylation of Terminal Olefinsa
a Reaction conditions: 5 mol % Pd(OAc)2 (0.05 mmol), 5 mol % 1 (0.05 mmol), 20 mol % NaOAc (0.20 mmol), substrate (1.0 mmol), dioxane (2.8 mL), AcOH (0.9 mL, 16 mmol), 1 atm O2, 60 °C. b Based on GC analysis of the crude reaction mixture. c Isolated yields. GC yields are given in parentheses. d A 3:1 mixture of allylic and homoallylic acetates was obtained. e Using 4 atm O2. A 5:1 mixture of linear and branched isomers was obtained.
Scheme 2. Net Anti-Markovnikov Hydration of Terminal Alkenes via a One-Pot, Three-Step Sequence
removal of the acetate under basic conditions, and hydrogenation of the alkene (Scheme 2A). No additional catalyst is required for the hydrogenation step; addition of activated carbon to the crude reaction mixture, which still contains Pd from the acetoxylation reaction, and stirring under 1 atm H2 results in efficient hydrogenaJ. AM. CHEM. SOC.
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tion of the alkene. Good yields of terminal alcohols were obtained for three representative substrates utilizing this sequence (Scheme 2B). The isolated yield of the alcohol essentially matched that of the initial acetoxylation step. Mechanistic studies have begun to provide insights into the ability of the diazafluorenone ligand 1 to support aerobic BQ-free catalytic turnover. Two similar [(L)PdII(η3-allyl)]OAc complexes, 4 (L ) 1) and 5 (L ) tBu2bpy), were prepared in order to compare the effects of O2 and BQ on the reactivity of the π-allyl-PdII complexes under catalytically relevant conditions (Figures 1 and 2). In the first set of experiments, the ability of 4 and 5 to undergo stoichiometric acetoxylation of the allyl ligand was probed by 1H NMR spectroscopy under three separate conditions: in the absence of an oxidant (i.e., under 1 atm N2), under 3 atm O2,13 and in the presence of 2 equiv of BQ (Figure 1). The diazafluorenone complex reacted to form allyl acetate in good yield under all these conditions (70-90%); however, the reaction time varied from 24 h (N2) to 3 h (O2) to 1 h (BQ).14 Complex 5, with the catalytically incompetent tBu2bpy ligand, was completely unreactive in the presence of N2 and O2; however, it underwent acetoxylation in the presence of 2 equiv of BQ (88%). A second set of experiments probed the possibility of reversible C-O bond formation by monitoring the ability of π-allyl-PdII complexes 4 and 5 to mediate acetate-d3 incorporation into cinnamyl acetate (Figure 2A). The proposed Pd-mediated mechanism for acetate exchange is shown in Figure 2B, and the data are summarized in Figure 2C. Diazafluorenone complex 4 mediated extensive acetate exchange (76% in 3 h) in the absence of an oxidant; however, this reactivity was eliminated by the presence of O2 or BQ.15 The extent of acetate exchange decreased systematically as the O2 pressure was increased (Figure 2D), presumably reflecting the ability of O2 to trap the Pd0-alkene complex (kox in Figure 2B) and inhibit exchange. Negligible acetate exchange was observed with tBu2bpy complex 5, even in the absence of an oxidant. These results provide insights into the catalytic steps that have been proposed to involve BQ (Scheme 1, steps II and III). The reactivity of 5 in the stoichiometric acetoxylation study (Figure 1) reveals that BQ can induce acetoxylation of an otherwise unreactive π-allyl-PdII complex. O2 is not an effective BQ surrogate in this reaction. The stoichiometric reactivity of 4 reveals that BQ is not required for the C-O bond-forming step when diazafluorenone is the ancillary ligand. We speculate that the distorted bite angle of the diazafluorenone ligand16 destabilizes PdII and allows the π-allyl ligand to undergo nucleophilic attack in the absence of BQ. Computational studies to probe this hypothesis will be the focus of future studies. The qualitative rate differences for the acetoxylation of 4 in the presence of N2, O2, and BQ (Figure 1) can be rationalized in two ways. One possibility is that O2 and BQ can enhance the rate by trapping the putative Pd0-alkene species and preventing reversion to the π-allyl-PdII complex.17 Alternatively, the higher rate with BQ than with O2 could reflect the ability of BQ to promote acetoxylation of the π-allyl-PdII complex in addition to trapping the Pd0 intermediate. Further work will be needed to probe the effect of ancillary ligands on other steps of the catalytic mechanism, such as C-H activation, and their influence on the identity of the turnover-limiting step and the catalyst resting state. Nevertheless, the results presented here provide clues into the ability of an ancillary ligand to enable catalytic turnover with O2 instead of BQ as the stoichiometric oxidant, and a plausible catalytic cycle is shown in Scheme 3. This study points to a potentially versatile ligand-based strategy to achieve aerobic Pd-catalyzed C-H oxidation. For example, BQ 15118
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Figure 1. Ligand effects on stoichiometric acetoxylation of well-defined
π-allyl-Pd complexes in the absence of an oxidant (under 1 atm N2) and in the presence of O2 (3 atm) and benzoquinone (2 equiv). The times given in parentheses are the reaction times needed for >95% conversion of 4 or 5.
Figure 2. Experiments designed to probe the reversibility of C-O bond formation from (L)Pd(η3-allyl) complexex. (A) Acetate exchange into cinnamyl acetate in the presence of a (L)Pd(η3-allyl) complex; (B) Mechanistic basis for (L)Pd(η3-allyl)-catalyzed acetate exchange in cinnamyl acetate and the influence of an oxidant on the extent of exchange; (C) Extent of acetate exchange with different (L)Pd(η3-allyl) complexes in the absence and presence of an oxidant; (D) O2 pressure effects on the extent of acetate exchange for the reaction in Figure 2A [(L)Pd(η3-allyl) ) 4].
and other oxidants have been proposed to promote C-C reductive elimination in oxidative cross-coupling reactions.3g,j,k On the basis
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(8)
of the present results, we anticipate that it might be possible to identify ancillary ligands that facilitate reductive elimination from PdII and thereby eliminate the requirement for undesirable stoichiometric oxidants in these reactions as well. Efforts to test this hypothesis have been initiated. Acknowledgment. We are grateful to the NIH (R01-GM67163 to S.S.S.; F32-GM087890 to A.N.C.) and the Camille and Henry Dreyfus Postdoctoral Program in Environmental Chemistry for financial support of this work. High-pressure instrumentation was supported by the NSF (CHE-0946901).
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Supporting Information Available: Experimental procedures, screening data, characterization data for all new compounds, and crystallographic data (CIF). This material is available free of charge via the Internet at http://pubs.acs.org. References (1) This subject has been extensively reviewed in recent years. For leading references, see the February 2010 issue of Chemical ReViews. (2) For recent reviews, see: (a) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48, 5094–5115. (b) Lyons, T. W.; Sanford, M. S. Chem. ReV. 2010, 110, 1147–1169. (c) Sun, C.-L.; Li, B.J.; Shi, Z.-J. Chem. Commun. 2010, 46, 677–685. (3) The precise outcome of reactions between oxidants and organo-PdII species varies depending on the oxidant and Pd species. In some cases, the oxidant generates a PdIV or PdIII intermediate, whereas in other cases it is not known whether the formal oxidation state of Pd changes. For important leading references, see: (a) Ba¨ckvall, J.-E.; Gogoll, A. Tetrahedron Lett. 1988, 29, 2243–2246. (b) Canty, A. J. Acc. Chem. Res. 1992, 25, 83–90. (c) Seligson, A. L.; Trogler, W. C. J. Am. Chem. Soc. 1992, 114, 7085–7089. (d) Szabo´, K. J. Organometallics 1998, 17, 1677–1686. (e) Dick, A. R.; Kampf, J. W.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127, 12790–12791. (f) Giri, R.; Chen, X.; Yu, J. Q. Angew. Chem., Int. Ed. 2005, 44, 2112–2115. (g) Chen, X.; Li, J.-J.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128, 78–79. (h) Stuart, D. R.; Villemure, E.; Fagnou, K. J. Am. Chem. Soc. 2007, 129, 12072–12073. (i) Stuart, D. R.; Fagnou, K. Science 2007, 316, 1172–1175. (j) Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 9651–9653. (k) Lanci, M. P.; Remy, M. S.; Kaminsky, W.; Mayer, J. M.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 15618–15620. (l) Powers, D. C.; Ritter, T. Nat. Chem. 2009, 1, 302–309. (m) Powers, D. C.; Geibel, M. A. L.; Klein, J. E. M. N.; Ritter, T. J. Am. Chem. Soc. 2009, 131, 17050–17051. (n) Khusnutdinova, J. R.; Rath, N. P.; Mirica, L. M. J. Am. Chem. Soc. 2010, 132, 7303–7305. (4) For advances in Pd-catalyzed aerobic oxidation reactions, see: (a) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400–3420. (b) Nishimura, T.; Uemura, S. Synlett 2004, 201–216. (c) Stoltz, B. M. Chem. Lett. 2004, 33, 362–367. (d) Stahl, S. S. Science 2005, 309, 1824–1826. (e) Gligorich, K. M.; Sigman, M. S. Chem. Commun. 2009, 3854–3867. (5) For a continuous-flow process that enables safe and scalable Pd-catalyzed aerobic oxidations, see: Ye, X.; Johnson, M. D.; Diao, T.; Yates, M. H.; Stahl, S. S. Green Chem. 2010, 12, 1180–1186. (6) For discussion of Pd0 oxidation by O2, see: (a) Muzart, J. Chem.sAsian J. 2006, 1, 508–515. (b) Stahl, S. S.; Thorman, J. L.; Nelson, R. C.; Kozee, M. A. J. Am. Chem. Soc. 2001, 123, 7188–7189. (c) Konnick, M. M.; Guzei,
(12) (13) (14)
(15)
I. A.; Stahl, S. S. J. Am. Chem. Soc. 2004, 126, 10212–10213. (d) Konnick, M. M.; Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 5753–5762. (e) Popp, B. V.; Stahl, S. S. Chem.sEur. J. 2009, 15, 2915–2922. For example, see: (a) Vargaftik, M. N.; Moiseev, I. I.; Syrkin, Y. K.; Yakshin, V. V.; Lomonosov, M. V. IzV. Akad. Nauk SSSR 1962, 5, 930– 931. (b) Kitching, W.; Rappoport, Z.; Winstein, S.; Young, W. G. J. Am. Chem. Soc. 1966, 88, 2054–2055. (c) Kikukawa, K.; Sakai, K.; Asada, K.; Matsuda, T. J. Organomet. Chem. 1974, 77, 131–145. (d) Heumann, A.; Åkermark, B. Angew. Chem., Int. Ed. Engl. 1984, 23, 453–454. (e) McMurry, J. E.; Kocˇotovsky´, P. Tetrahedron Lett. 1984, 25, 4187–4190. (f) Jia, C.; Mu¨ller, P.; Mimoun, H. J. Mol. Catal. A: Chem. 1995, 101, 127–136. (g) El Firdoussi, L.; Baqqa, A.; Allaoud, S.; Allal, B. A.; Karim, A.; Castanet, Y.; Mortreux, A. J. Mol. Catal. A: Chem. 1998, 135, 11–22. (h) Grennberg, H.; Ba¨ckvall, J.-E. Chem.sEur. J. 1998, 4, 1083–1089. (i) Attolini, M.; Peiffer, G.; Maffei, M. Tetrahedron 2000, 56, 2693–2697. (a) Chen, M. S.; White, M. C. J. Am. Chem. Soc. 2004, 126, 1346–1347. (b) Chen, M. S.; Prabagaran, N.; Labenz, N. A.; White, M. C. J. Am. Chem. Soc. 2005, 127, 6970–6971. (c) Mitsudome, T.; Umetani, T.; Nosaka, N.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. Angew. Chem., Int. Ed. 2006, 45, 481–485. (d) Lin, B.-L.; Labinger, J. A.; Bercaw, J. E. Can. J. Chem. 2009, 87, 264–271. (e) Pilarski, L. T.; Selander, N.; Bo¨se, D.; Szabo´, K. J. Org. Lett. 2009, 11, 5518–5521. (f) Henderson, W. H.; Check, C. T.; Proust, N.; Stambuli, J. P. Org. Lett. 2010, 12, 824–827. (g) Thiery, E.; Aouf, C.; Belloy, J.; Harakat, D.; Le Bras, J.; Muzart, J. J. Org. Chem. 2010, 75, 1771–1774. For leading references to other advances in Pd-catalyzed allylic C-H oxidation, see: (a) Fraunhoffer, K. J.; White, M. C. J. Am. Chem. Soc. 2007, 129, 7274–7276. (b) Liu, G.; Yin, G.; Wu, L. Angew. Chem., Int. Ed. 2008, 47, 4733–4736. (c) Vermeulen, N. A.; Delcamp, J. H.; White, M. C. J. Am. Chem. Soc. 2010, 132, 11323–11328. (d) Yin, G.; Wu, Y.; Liu, G. J. Am. Chem. Soc. 2010, 132, 11978–11987. Grennberg, H.; Gogoll, A.; Ba¨ckvall, J.-E. Organometallics 1993, 12, 1790– 1793. For example, see: (a) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. Tetrahedron Lett. 1998, 39, 6011–6014. (b) Fix, S. R.; Brice, J. L.; Stahl, S. S. Angew. Chem., Int. Ed. 2002, 41, 164–166. (c) Nishimura, T.; Araki, H.; Maeda, Y.; Uemura, S. Org. Lett. 2003, 5, 2997–2999. (d) Andappan, M. M. S.; Nilsson, P.; Larhed, M. Chem. Commun. 2004, 218–219. (e) Sheldon, R. A.; Arends, I. W. C. E.; ten Brink, G.-J.; Dijksman, A. Acc. Chem. Res. 2002, 35, 774–781. (f) Yoo, K. S.; Park, C. P.; Yoon, C. H.; Sakaguchi, S.; O’Neill, J.; Jung, K. W. Org. Lett. 2007, 9, 3933–3935. (g) Zhang, Y.-H.; Shi, B.-F.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 5072– 5074. (a) Haggin, J. Chem. Eng. News 1993, 71 (22), 23–27. (b) Beller, M.; Seayad, J.; Tillack, A.; Jiao, H. Angew. Chem., Int. Ed. 2004, 43, 3368– 3398. Poor gas-liquid mixing in 5 mm NMR tubes required the use of 3 atm O2 to ensure the presence of ∼1 equiv of dissolved O2 in solution. In the absence of oxidant, Pd black was observed at the end of the reaction, whereas the reaction mixture remained homogeneous in the presence of oxidant, presumably as a result of the formation of ligated PdII(OAc)2 species. Separately, it was noted that the reaction of 4 was unaffected by the presence of excess ligand 1 (5 equiv) in solution, suggesting that formation of allyl acetate does not proceed via pre-equilibrium dissociation of 1 from the Pd center. Lin et al.8d previously reported that the (bpm)Pd(η3-cinnamyl) complex 6 mediates acetate exchange in cinnamyl acetate in the absence of an oxidant (eq 2):
In addition, they demonstrated that 6 is stable toward stoichiometric acetoxylation under N2 but releases cinnamyl acetate in the presence of BQ under conditions somewhat different from ours (AcOH, 80 °C) (cf. Figure 1). The reactivity of 6 in the presence of O2 was not reported. Preliminary studies have suggested that (bpm)Pd(allyl) complexes react differently under our conditions. Further work will be needed to make a direct comparison between ligand 1 and bipyrimidine in allylic acetoxylation reactions. (16) The BF4- salts of 4 and 5 were characterized by X-ray crystallography. For a summary of the structural data, see Figure S6 and the additional data in the Supporting Information. (17) Previous studies in our lab have demonstrated the reaction of O2 with Pd0alkene complexes to afford η2-peroxo species relevant to this process. See ref 6b and: (a) Popp, B. V.; Thorman, J. L.; Stahl, S. S. J. Mol. Catal. A: Chem. 2006, 251, 2–7. (b) Popp, B. V.; Morales, C. M.; Landis, C. R.; Stahl, S. S. Inorg. Chem. 2010, 49, 8200–8207.
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